Cancer is the leading cause of death in most developed countries, and as the average age of the population continues to rise, so do the numbers of diagnosed cases of cancer. Cancer is characterized by uncontrolled growth and spread of abnormal cells. Despite advances in cancer diagnosis and treatment over the years, existing therapies still have limitations. Surgery and radiotherapy, for example, may be curative only if the cancer is diagnosed early enough, while current drug therapies, e.g., for metastatic diseases, seldom offer a long-term cure. Over the last decade, new strategies to treat cancer patients have emerged. Unlike traditional cytotoxic therapies, the new strategies focus more on the tumor itself and its supportive microenvironment. Additional approaches for cancer treatment include preventing angiogenesis and activating the immune system, for example using cancer vaccines and cell therapies. The main aim is to improve anti-tumor efficacy while reducing toxic and other adverse effects in the patients. However, even with new therapies entering the market, there is an unmet medical need for new drugs effective as monotherapy or in combination with existing agents as a first line therapy in various types of cancer, and as second and third line therapies in treatment of resistant tumors.
For example, lung cancer is one of the most fatal cancers worldwide, causing more than 1.2 million deaths each year, according to recent reports. Non-small cell lung cancer (NSCLC) cases are the vast majority of all cases of lung cancer. NSCLC is particularly fatal since most of the patients are diagnosed when the disease has already progressed to a relatively advanced stage, usually at incurable stages IIIB or IV. According to an analysis done by the International Association for the Study of Lung Cancer (IASLC), the 5-year survival rate is 73% at stage IA, 58% at stage IB, 46% at stage IIA, 36% at stage IIB and only 24% if patient was diagnosed at stage IIIA of NSCLC disease. Besides the need for earlier diagnosis, there is a great need for additional, more effective, therapies. In resected NSCLC, the only approved adjuvant therapy is chemotherapy using drugs such as paclitaxel, cisplatin, and vinblastine, which provide a limited clinical benefit. In completely resected NSCLC, for example, an absolute benefit of elevating 5-year survival rate by only 5.4% (on average) was demonstrated in a pooled analysis of five large trials of adjuvant cisplatin-based chemotherapy carried out by the LACE collaborative group. Moreover, 34% of the patients in these trials did not complete the planned number of cycles due to toxicity, treatment-emergent adverse events, and adverse effects. The benefit of chemotherapy treatment is still under debate for stage I.
As another example, melanoma, a disease which occurs when melanocytes undergo mutational changes and become malignant, causes about 50,000 deaths annually worldwide, and its incidence continues to increase. The incidence of malignant melanoma has increased fivefold from 1980 to 2009. If the tumor is detected early, before invading the dermis, surgical excision is curative in approximately 99% of patients. Unfortunately, melanoma is not always diagnosed at early stage, resulting in poor prognosis. Currently, the main treatments for melanoma are surgery, radiotherapy and chemotherapy. Surgery can provide efficient tumor resection and cure the patient if there are no metastases. Radiation therapy is used in severe cases, and in conjunction with surgery, to increase the efficiency of treatment. Enormous advances in the treatment of melanoma have occurred in recent years as a result of improved understanding of the molecular pathways driving this malignancy as well as the critical importance of the role of the immune system in this process. However, there still remains a need for more effective and safer melanoma therapies.
U.S. Pat. No. 6,468,537 discloses peptides derived from nucleosomal histone proteins which are useful for delaying the onset and progression of systemic lupus erythematosus. Among other peptides, a peptide of the sequence Leu-Arg-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Val-Gly-Ala-Gly-Ala-Pro (SEQ ID NO: 9 of U.S. Pat. No. 6,468,537) is disclosed.
U.S. Pat. Nos. 7,238,656 and 7,528,227 disclose, inter alia, histone H2A-derived peptides and derivatives thereof, and use of these peptides and derivatives for treating inflammatory diseases. Among other peptides, a peptide of the sequence H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH is disclosed (SEQ ID NO: 13 of U.S. Pat. No. 7,238,656, SEQ ID NO: 1 of U.S. Pat. No. 7,528,227).
There remains an unmet need for safe and efficient agents that are useful in treating malignant proliferative diseases, having reduced or no side effects.